The future islet research of our laboratory has at last two major objectives: 1) To thoroughly test the glucokinase glucose-sensor hypothesis of glucose recognition by beta cells, to study the implication of this concept for islet biochemistry and physiology and to evaluate other unique metabolic design features of islet cells, as for instance the role of the alpha-glycero-P shuttle in glucose stimulated insulin release. 2) To study the role of glucose and amino acids in beta cell hypertrophy and hyperplasia that are typical for obesity syndromes, to assess the involvement of these fuels in the fetal and postnatal islet development, to explore the nature of the adaptive beta cell responses for hormonal and environmental influences and to explain cases with a failure to adapt. A wide gamout of approaches and technologies are to be employed. They include the isolated perfused pancreas, collagenase isolated islets, islet cell tissue culture, quantitative histochemistry, enzymatic fluorimetry, radiometric micro assays for glucokinase and hexokinase and two-dimensional, high resolution SDS-PAGE of biosynthetically labeled proteins combined with computer image analysis and data management. Pevious work from our laboratory has helped to set the stage for the present plans and it is anticipated that the work proposed will settle several fundamentally important issues in islet cell research.